frailty

引言“It's always ok in the end, and it's not ok, it's not the end.”——《终结疾病》2020年，一部名为《终结疾病》（Ending disease）的纪录片上映，影片讲述了10个普通家庭参与第一代干细胞疗法并与癌症、艾滋病、瘫痪和失明等严重疾病抗争的故事。过去，这些难以预见，令人绝望的病症存在着广泛的临床难题。随着生物学技术的发展，干细胞疗法带来了新的希望。干细胞是一类未分化的细胞，具有多向分化潜能和自我更新能力，这种近乎“万用”的表现，赋予了干细胞疗法和再生医学以无尽想象力。然而，新生事物的发展并不总是一帆风顺，令人振奋的科研结果不是全部，干细胞研究者的热情与挑战、患者的期待与迷茫、市场的火热与混乱、政策的鼓励与审慎，在这数十年间相互交织，无时无刻不在影响着这一新兴疗法的发展及应用。谈到这些，汤红明的体会尤其深刻，干细胞极其复杂，这不仅体现在科学研究方面，更涉及产业链条上的每个环节和所有参与者。汤红明：现任同济大学附属东方医院干细胞基地办公室主任，兼任国家干细胞转化资源库副主任、细胞治疗临床研究中心执行主任、张江国家自主创新示范区干细胞转化医学产业基地办公室主任、上海干细胞临床转化研究院办公室主任、《医学参考报》干细胞与再生医学专刊编辑部主任。自 2015 年调到上海张江国家自主创新示范区干细胞转化医学产业基地（东方医院）后，汤红明助力东方医院在干细胞领域的超前布局，深耕该领域近10年，以第一作者或通信作者在中华医学系列期刊发表干细胞领域系列管理论文12篇（内容涵盖建库、临床研究推进、质量控制/风险防控、学术/伦理审查、成果转化、产业化等），获授权干细胞领域发明专利14项。公开资料显示，全球干细胞技术专利地域分布主要集中在中美两地，我国的干细胞产业发展处于世界领先地位。不过从20世纪90年代步入临床转化应用的今天，干细胞获批上市的产品却并不多。以中美两国为例，我国的干细胞疗法还停留在临床试验阶段，并没有产品获批上市，而美国批准的干细胞产品也主要集中于造血干细胞移植治疗血液病的相关技术和产品。此外，欧盟、日本、韩国和伊朗等国虽然在审批上表现得更加激进，批准了多个间充质干细胞药物，但在市场表现、适应证覆盖以及对患者的影响方面仍然处于起步阶段，这与人们通常理解的作为“万用细胞”的干细胞可以多向分化的极具想象力的应用前景显然是有落差的。在干细胞领域长期的临床研究管理工作，使得汤红明对这一现象有着更加冷静的思考与观察。有一种广泛并长期存在的观点认为，干细胞领域发展缓慢是由于各国政府监管政策过于谨慎导致的。“我不这么认为”，汤红明说，“干细胞产业的蓬勃发展是多方面因素共同作用的结果，这要求政府、科研院所、研发机构、企业、医疗机构、金融机构等单位之间进行紧密的合作与协调。在这一过程中，各方必须发挥其独特的作用，共同构建一个互补、协同的生态系统。相应地，产业进程中出现的问题也往往是多方面因素共同作用的结果，不应简单归咎于单一环节。”“无论在美国、中国还是世界上其他国家，政策因素只是影响干细胞成药的一个方面，而在干细胞成药的全过程，包括法规、指南、工艺、质量管理、Pre-IND、IND、临床试验、上市等这一整条线上，所有环节的参与者都有责任。”“再比如，按照药物试验管理规范，如果能做出一款有效性和安全性都过硬的干细胞药物，我相信政策从来都不是问题”。这也从另一方面反映出了干细胞产品成药所面临的真正困难，就是如何在可靠的科学研究和临床试验过程下，证明其安全性和有效性。比如针对抗衰老研究的干细胞制剂，目前来看就很难有成药机会，虽然相关的研究和临床实践有很多良好案例，但目前的药物注册需要针对某一具体疾病，而衰老并不是，哪怕是针对衰弱症进行研究并将之联系到抗衰老方向，目前来看也少有机构主体可以付出巨大的时间和资源成本来获得经得住药品注册规范检验的数据和成果。那么，这是否影响了干细胞研究的热情？答案是否定的。我国干细胞研究起步较早，早在20世纪90年代我国就推出了一系列政策及法规文件，以推动产业发展。经过30年沉浮，有过成绩也有过乱象。目前我国对于干细胞领域的监管明确按照药品与医疗技术“双轨制”执行，分别是上面提到的药品注册路径和医疗技术路径。截至目前，按照药品注册路径，我国已有114个干细胞制剂获IND申请受理，尚未有干细胞药物上市，对比CAR-T免疫细胞疗法作为药物上市的成功案例，该路径是我国目前干细胞产品向临床转化的唯一路径。而另一条作为生物医学新技术路径，在2019年发布的《生物医学新技术临床应用管理条例（征求意见稿）》中明确干细胞、体细胞技术临床转化应用，监督管理的实施细则，由国家卫生健康主管部门和国家药品监督管理部门制定，但后续该意见稿未正式发布，这条路径一直处于中断状态。目前，除了药物研发，干细胞临床研究可按照《干细胞临床研究管理办法（试行）》，开展机构与项目双备案的临床研究。目前，国内已有148家医疗机构和152项目干细胞临床研究完成国家备案，其研究形式和研究者发起的临床研究（IIT）相似，研究结果可以作为药物申报材料。可见，干细胞临床研究备案现在仅作为干细胞药物研发试验的一种补充策略。针对这一现况，国内一些专家和企业也支持仅以药品注册路径为干细胞疗法的唯一转化路径。对此，汤红明认为不宜一刀切。原因是包括美国、德国、日本等发达国家，分别存在州立法、豁免条款、双轨制等将干细胞疗法作为技术应用的路径，这主要基于干细胞移植治疗这一技术本身的科学原因。干细胞是每个人身体中富含的一种细胞，其来源人体自身，每个人又是独特的，这和传统的化学药物、生物制剂的成药理念不太一样：首先是来源受供体影响而难以标准化；其次是干细胞制剂是活细胞，其在体内的作用机制不是单一的；再次是生产形式和产量受到限制，无法大规模均一化生产。如造血干细胞疗法，其作为一种医疗技术已经成功挽救了无数的生命。一些自体和异体的间充质干细胞疗法也经过了20多年的临床研究，其风险基本可预估和可防控。而且随着基础研究的不断深入与突破，间充质干细胞疗法的机制和代谢路径也在逐步清晰。随着经济发展和人民日益增高的健康需求，我国干细胞产业的研发、生产和市场容量需求亟需得到释放，盲目的一刀切，可能使得干细胞转化应用的速度再次落后于欧美日等发达国家和地区，让一些有需求也愿意尝试的患者被迫选择出国接受治疗或者接受不正规的治疗。汤红明建议，对于干细胞技术治疗疾病，可根据细胞来源、技术特点及临床应用等方面的难度，进行风险分级管理，通过安全性与有效性验证后，探索低风险项目按医疗技术的临床转化路径实施。并在此基础上，逐步加强和完善研究者发起的临床研究（IIT）与药企发起的临床试验（IST）的并轨管理，建立和完善IIT临床数据和成果用于新药注册申请的机制和路径，最终打通医疗技术双备案制度的转化路径。“东方医院是首批完成国家干细胞临床研究机构备案的医疗机构，截至目前，东方医院已有7项国家干细胞临床研究备案项目（适应证为心衰、间质性肺病、2型糖尿病肾病、帕金森病）和1项科技部新冠应急项目，今后将在更多的疾病领域探索干细胞的临床转化。”，汤红明介绍。如今，东方医院的干细胞产业基地已经完全超越了传统的医院学科建设范畴，成为国内首个国际领先的集干细胞前沿基础研究、临床前研究、临床研究、临床转化与应用全产业链为一体的干细胞研究高地。对于干细胞产业的未来发展，虽然没能直接发问，但采访时汤主任回答中透露出的冷静与思考已经给了我们答案。就像开头提到的纪录片中一位母亲安慰女儿时所说的，“It's always ok in the end, and it's not ok, it's not the end.”“希望中国的干细胞技术能真正实现临床转化，加速突破干细胞转化过程中的关键瓶颈，让人民群众能从干细胞技术中受益”，汤红明表示。第四届基因与细胞治疗青藜风云论坛CGCT2024年第四届基因与细胞治疗青藜风云论坛（CGCT 2024），由中国研究型医院学会医工转化与健康产业融合专业委员会、博腾生物、佰傲谷BioValley联合主办，将于2024年7月5-6日在上海召开。本次大会，同济大学附属东方医院干细胞基地办公室主任/国家干细胞转化资源库副主任汤红明将出席论坛二“干细胞及再生医学分论坛”，与大家分享更多细胞前沿内容！希望所有与会嘉宾都能满载而归，一起助力CGT产业界发展。议程框架 CGCT 2024心动不如行动，欢迎各位老师前来交流学习！👆扫码报名，虚位以待👆*具体嘉宾请以会议当天现场为准点击"阅读原文"，进入大会官网报名&了解更多资讯~

Phase 2b clinical trial evaluating Lomecel-BTM in rare pediatric disease HLHS on track for completing enrollment by end of 2024Data from Phase 2a clinical trial evaluating Lomecel-BTM in Alzheimer’s Disease selected for Featured Research Oral Presentation at 2024 Alzheimer’s Association International ConferenceCompleted two financings in April raising gross proceeds of $11.4 million to fund continued clinical developmentFocused expenditure management reduced first quarter Total Operating Expenses 8% year-over-yearCompany to host conference call and webcast today at 5:00pm ET MIAMI, May 14, 2024 (GLOBE NEWSWIRE) -- Longeveron Inc. (NASDAQ: LGVN), a clinical stage regenerative medicine biotechnology company developing cellular therapies for life-threatening and chronic aging-related conditions, today reported financial results for the quarter ended March 31, 2024 and provided a business update. “In the first quarter, we continued to focus on advancing our cutting-edge cellular therapy research and its application through our investigational product candidate, Lomecel-BTM, in Hypoplastic Left Heart Syndrome (HLHS) and Alzheimer’s disease, both of which are devastating for impacted patients and their families,” said Wa’el Hashad, Chief Executive Officer of Longeveron. “Based on the strength of the data from our positive Phase 1 study in HLHS, we are excited to complete enrollment in our on-going Phase 2b study by the end of this year. The Phase 1 data was the basis for the U.S. FDA awarding the HLHS program with three distinct and important designations: Orphan Drug designation, Fast Track designation, and Rare Pediatric Disease designation, which, upon approval, may lead to granting of a Priority Review Voucher, a very valuable additional asset. Lastly, in April, we raised $11.4 million of gross proceeds from equity transactions, with participation from certain board members and insiders of the Company, to fund continued clinical development of Lomecel-B.” Development Programs UpdateLongeveron’s lead investigational therapeutic candidate is Lomecel-BTM, a proprietary, scalable, allogenic cellular therapy being evaluated in multiple indications. Hypoplastic Left Heart Syndrome (HLHS) – a rare pediatric congenital heart birth defect in which the left ventricle (one of the pumping chambers of the heart) is either severely underdeveloped or missing. On-going Phase 2b clinical trial (ELPIS II) enrolling 38 pediatric patients, with enrollment completion anticipated by year end 2024ELPIS II is being conducted in collaboration with the National Heart, Lung, and Blood Institute (NHLBI) through grants from the National Institutes of Health (NIH)ELPIS II builds on the positive clinical results of ELPIS I, in which children in the trial experienced 100% transplant-free survival up to five years of age after receiving Lomecel-BTM compared to approximate 20% mortality rate observed from historical control dataThe Company intends to request a Type B meeting with the U.S. Food and Drug Administration (FDA) to discuss development strategy for HLHS and expectations for the potential Biologics License Application (BLA) approval Alzheimer’s Disease (AD) – a neurodegenerative disorder that leads to progressive memory loss and death and currently has very limited therapeutic options. In a completed Phase 2a clinical trial (CLEAR MIND), Lomecel-B™ treated patients showed an overall slowing/prevention of disease worsening compared to placebo. The trial achieved the primary safety and secondary efficacy endpoints and showed statistically significant improvements in pre-specified clinical and biomarker endpoints in specific Lomecel-B™ groups compared to placeboThese results support the therapeutic potential of Lomecel-BTM in the treatment of mild Alzheimer’s disease and provided evidence-based support for further clinical developmentFull results from the CLEAR MIND study have been selected for a featured research oral presentation at the 2024 Alzheimer's Association International Conference (AAIC)The Company anticipates meeting with the FDA to review future clinical and regulatory strategy Recent Corporate Highlights In January 2024, the United States Patent and Trademark Office mailed a notice of allowance to the Company for its United States patent application with claims directed to methods for use of allogeneic human mesenchymal stem cells as an adjuvant to benefit patients with Aging-related Frailty who are receiving vaccines for conditions such as Covid and the flu. (That application issued as U.S. Patent No. 11,975,068, on May 7, 2024.)In April, the Company completed two capital raises which resulted in gross proceeds of $11.4 million. First Quarter 2024 Summary Financial Results Revenues, Cost of Revenues and Gross Profit: Revenues for the three months ended March 31, 2024 and 2023 were $0.5 million and $0.3 million, respectively. 2024 revenues increased $0.2 million, or 96%, when compared to 2023 mainly as a result of increased participant demand for our Bahamas Registry Trial. Grant revenue for the three months ended March 31, 2024 and 2023 was $0 and less than $0.1 million, respectively. Clinical trial revenue, which is derived from the Bahamas Registry Trial, for the three months ended March 31, 2024 and 2023 was $0.5 million and $0.2 million, respectively. Clinical trial revenue for the three months ended March 31, 2024 increased by $0.3 million, or 116%, when compared to 2023 as a result of increased participant demand. Contract manufacturing revenue for the three months ended March 31, 2024 and 2023 was less than $0.1 million and $0, respectively.Related cost of revenues: Cost of revenues was $0.2 million for the three-month periods ended March 31, 2024 and 2023. The increase of less than $0.1 million, or 8%, was primarily due to the increase in the revenues earned from the investigational Frailty and Cognitive Impairment registry trial in the Bahamas and reduced direct costs associated with our grants program. This resulted in a gross profit of approximately $0.3 million for the three months ended March 31, 2024, an increase of $0.2 million, or 333%, when compared with a gross profit of $0.1 million for 2023.General and Administrative Expenses: General and administrative expenses for the three months ended March 31, 2024 increased to approximately $2.2 million, compared to $2.0 million for the same period in 2023. The increase of approximately $0.2 million, or 9%, was primarily related to an increase in expenses related to professional fees.Research and Development Expenses: Research and development expenses for the three months ended March 31, 2024 decreased to approximately $2.2 million, from approximately $2.8 million for the same period in 2023. The decrease of $0.6 million, or 20%, was primarily due to a decrease of $0.6 million in research and development expenses being incurred for the Alzheimer’s disease clinical trial and reduced costs for the Aging-related Frailty clinical trial following our decision to discontinue trial activities in Japan, reduced cost of supplies of $0.3 million, and a decrease of $0.2 million in equity-based compensation expenses allocated to research and development expenses. These reductions were partially offset by $0.4 million of higher compensation and benefit costs.Other Expense (Income), net: Other income for the three months ended March 31, 2024 was less than $0.1 million. Other income consisted of less than $0.1 million from interest earned on money market funds and marketable securities. Other income for the three months ended March 31, 2023 was $0.1 million as result of gains from marketable securities.Net Loss: Net loss decreased to approximately $4.1 million for the three months ended March 31, 2024 from a net loss of $4.6 million for the same period in 2023. The decrease in the net loss of $0.5 million, or 13%, was for the reasons outlined above.Cash and cash equivalents and marketable securities as of March 31, 2024 were $2.3 million. In April 2024, the Company completed two capital raises which resulted in gross proceeds of $11.4 million. The Company believes its existing cash and cash equivalents will enable it to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2024. These estimates are based on assumptions that may prove to be imprecise, and the Company could utilize its available capital resources sooner than it expects. Conference Call and Webcast The Company will host a conference call and webcast today at 5:00 p.m. ET. Conference Call Number: 1.877.407.0789Conference ID: 13745868Call meTM Feature: Click HereWebcast: Click Here An archived replay of the webcast will be available on the “Events & Presentations” section of the Company’s website following the conference. About Longeveron Inc. Longeveron is a clinical stage biotechnology company developing regenerative medicines to address unmet medical needs. The Company’s lead investigational product is Lomecel-B™, an allogeneic medicinal signaling cell (MSC) therapy product isolated from the bone marrow of young, healthy adult donors. Lomecel-B™ has multiple potential mechanisms of action encompassing pro-vascular, pro-regenerative, anti-inflammatory, and tissue repair and healing effects with broad potential applications across a spectrum of disease areas. Longeveron is currently pursuing three pipeline indications: hypoplastic left heart syndrome (HLHS), Alzheimer’s disease, and Aging-related Frailty. For more information, visit www.longeveron.com or follow Longeveron on LinkedIn, X, and Instagram. Forward-Looking Statements Certain statements in this press release that are not historical facts are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, which reflect management’s current expectations, assumptions, and estimates of future operations, performance and economic conditions, and involve risks and uncertainties that could cause actual results to differ materially from those anticipated by the statements made herein. Forward-looking statements are generally identifiable by the use of forward-looking terminology such as “believe,” “expects,” “may,” “looks to,” “will,” “should,” “plan,” “intend,” “on condition,” “target,” “see,” “potential,” “estimates,” “preliminary,” or “anticipates” or the negative thereof or comparable terminology, or by discussion of strategy or goals or other future events, circumstances, or effects and include, but are not limited to, the anticipated use of proceeds from the private placement. Factors that could cause actual results to differ materially from those expressed or implied in any forward-looking statements in this release include, but are not limited to, market and other conditions, our limited operating history and lack of products approved for commercial sale; adverse global conditions, including macroeconomic uncertainty; inability to raise additional capital necessary to continue as a going concern; our history of losses and inability to achieve profitability going forward; the absence of FDA-approved allogenic, cell-based therapies for Aging-related Frailty, AD, or other aging-related conditions, or for HLHS or other cardiac-related indications; ethical and other concerns surrounding the use of stem cell therapy or human tissue; our exposure to product liability claims arising from the use of our product candidates or future products in individuals, for which we may not be able to obtain adequate product liability insurance; the adequacy of our trade secret and patent position to protect our product candidates and their uses: others could compete against us more directly, which could harm our business and have a material adverse effect on our business, financial condition, and results of operations; if certain license agreements are terminated, our ability to continue clinical trials and commercially market products could be adversely affected; the inability to protect the confidentiality of our proprietary information, trade secrets, and know-how; third-party claims of intellectual property infringement may prevent or delay our product development efforts; intellectual property rights do not necessarily address all potential threats to our competitive advantage; the inability to successfully develop and commercialize our product candidates and obtain the necessary regulatory approvals; we cannot market and sell our product candidates in the U.S. or in other countries if we fail to obtain the necessary regulatory approvals; final marketing approval of our product candidates by the FDA or other regulatory authorities for commercial use may be delayed, limited, or denied, any of which could adversely affect our ability to generate operating revenues; we may not be able to secure and maintain research institutions to conduct our clinical trials; ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations; if we receive regulatory approval of Lomecel-B™ or any of our other product candidates, we will be subject to ongoing regulatory requirements and continued regulatory review, which may result in significant additional expense; being subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our therapeutic candidates; reliance on third parties to conduct certain aspects of our preclinical studies and clinical trials; interim, “topline” and preliminary data from our clinical trials that we announce or publish from time to time may change as more data become available and are subject to audit and verification procedures that could result in material changes in the final data; the volatility of price of our Class A common stock; we could lose our listing on the Nasdaq Capital Market; provisions in our certificate of incorporation and bylaws and Delaware law might discourage, delay or prevent a change in control of our company or changes in our management and, therefore, depress the market price of our Class A common stock; we have never commercialized a product candidate before and may lack the necessary expertise, personnel and resources to successfully commercialize any products on our own or together with suitable collaborators; and in order to successfully implement our plans and strategies, we will need to grow our organization, and we may experience difficulties in managing this growth. Further information relating to factors that may impact the Company’s results and forward-looking statements are disclosed in the Company’s filings with the Securities and Exchange Commission, including Longeveron’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission on February 27, 2024, as amended by the Annual Report on Form 10-K/A filed March 11, 2024, its Quarterly Reports on Form 10-Q, and its Current Reports on Form 8-K. The forward-looking statements contained in this press release are made as of the date of this press release, and the Company disclaims any intention or obligation, other than imposed by law, to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. Investor Contact:Derek ColeInvestor Relations Advisory Solutionsderek.cole@iradvisory.com Longeveron Inc.Condensed Balance Sheets(In thousands, except share and per share data) March 31,2024 December 31,2023 (Unaudited) Assets Current assets: Cash and cash equivalents $1,940 $4,949 Marketable securities 351 412 Prepaid expenses and other current assets 1,288 376 Accounts and grants receivable 178 111 Total current assets 3,757 5,848 Property and equipment, net 2,348 2,529 Intangible assets, net 2,263 2,287 Operating lease asset 1,139 1,221 Other assets 190 193 Total assets $9,697 $12,078 Liabilities and stockholders’ equity Current liabilities: Accounts payable $1,467 $638 Accrued expenses 2,401 2,152 Current portion of lease liability 601 593 Deferred revenue 826 506 Total current liabilities 5,295 3,889 Long-term liabilities: Lease liability 1,295 1,448 Other liabilities 66 - Total long-term liabilities 1,361 1,448 Total liabilities 6,656 5,337 Commitments and contingencies (Note 9) Stockholders’ equity: Preferred stock, $0.001 par value per share, 5,000,000 shares authorized, no shares issued and outstanding at March 31, 2024, and December 31, 2023. - - Class A Common Stock, $0.001 par value per share, 84,295,000 shares authorized, 1,034,283 shares issued and outstanding at March 31, 2024: 1,025,183 issued and outstanding, at December 31, 2023 1 1 Class B Common Stock, $0.001 par value per share, 15,705,000 shares authorized, 1,484,005 shares issued and outstanding at March 31, 2024: 1,485,560 issued and outstanding, at December 31, 2023 1 1 Additional paid-in capital 92,080 91,823 Stock subscription receivable - (100)Accumulated deficit (89,042) (84,984)Accumulated other comprehensive loss 1 - Total stockholders’ equity 3,041 6,741 Total liabilities and stockholders’ equity $9,697 $12,078 Longeveron Inc.Condensed Statements of Operations(In thousands, except per share data)(Unaudited) Three months endedMarch 31, 2024 2023 Revenues Clinical trial revenue $515 $238 Contract manufacturing revenue 33 - Grant revenue - 41 Total revenues 548 279 Cost of revenues 219 203 Gross profit 329 76 Operating expenses General and administrative 2,200 2,012 Research and development 2,219 2,780 Total operating expenses 4,419 4,792 Loss from operations (4,090) (4,716)Other income and (expenses) Other income, net 32 69 Total other income, net 32 69 Net loss $(4,058) $(4,647)Basic and diluted net loss per share $(1.61) $(2.21)Basic and diluted weighted average common shares outstanding 2,513,587 2,103,362 A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/455da66f-07a0-49fe-9b5d-6b82b97f6e89

Richard Kender, retired SVP of Business Development and Corporate Licensing for Merck & Co., Inc., has been appointed to the Longeveron BoardDr. Roger Hajjar, former head of R&D at Ring Therapeutics, has been nominated as a candidate for the Board, subject to election at the Company’s Annual Meeting of StockholdersNeha Motwani, former managing director and senior healthcare investment banker at William Blair, Truist, and Oppenheimer and Company, also has been nominated as a candidate for the Board, subject to election at the Company’s Annual Meeting of StockholdersExisting directors, Dr. Joshua Hare and Ursula Ungaro, have been nominated as candidates for re-election to the Board, subject to election at the Company’s Annual Meeting of StockholdersJeffrey Pfeffer and Cathy Ross have voluntarily resigned from the Board MIAMI, May 10, 2024 (GLOBE NEWSWIRE) -- Longeveron Inc. (NASDAQ: LGVN), a clinical stage regenerative medicine biotechnology company developing cellular therapies for life-threatening and chronic aging-related conditions, today announced planned transitions on its Board of Directors. Richard Kender, a retired Senior Vice President of Business Development and Corporate Licensing at Merck & Co., Inc., has joined the Longeveron Board of Directors. Mr. Kender spent his entire professional career at Merck in various corporate roles of increasing responsibility and was involved in more than 100 business development and licensing transactions. Mr. Kender was appointed by the Longeveron Board of Directors to fill the Board position vacated by Jeffrey Pfeffer who has voluntarily resigned and whose Board seat was not up for re-election in the upcoming Annual Meeting of Shareholders. The Board of Directors has also nominated Roger Hajjar, MD, former head of R&D at Ring Therapeutics, and Neha Motwani, a former senior healthcare investment banker, as nominees for the Board, along with existing directors Joshua Hare and Ursula Ungaro, subject to their respective elections at the Company’s upcoming 2024 Annual Meeting of Shareholders. Cathy Ross, who joined the Longeveron Board in February 2021 and whose term was expiring next month at this year’s annual meeting, voluntarily resigned from the Board in advance of the meeting. These transitions are part of the planned Board refreshment process at Longeveron, with a focus on bringing in new, relevant, experienced leaders over time to add to the knowledge base and experience provided by current and departing Board members. “On behalf of the entire Board and the Longeveron organization, I want to recognize and thank Jeffrey and Cathy for their leadership, service and countless contributions,” said Joshua Hare, M.D., Co-founder, Chief Science Officer and Chairman of the Board. “Their guidance and insights were critical to Longeveron navigating complex challenges and advancing our cellular therapy research. We wish them well in their future endeavors.” “Richard is a wonderful addition to our Board,” said Wa’el Hashad, Chief Executive Officer. “His industry experience and successful leadership of biopharmaceutical licensing transactions will bring tremendous value to Longeveron as we continue to advance Lomecel-B™, our proprietary cellular therapy that has generated positive data across multiple clinical trials. I look forward to collaborating with him to advance these important therapeutic development programs.” “I am excited to join the Longeveron Board at this important and exciting time for the company,” said Mr. Kender. “The promise of cellular therapy, and Lomecel-B™ in particular, positions the Company to potentially profoundly impact patients’ lives for the better by addressing numerous unmet medical needs across multiple devastating diseases.” Roger Hajjar, M.D., is an internationally recognized scientist whose cardiac gene therapy discoveries have spurred clinical trials for heart failure, and whose methodologies for cardiac-directed gene transfer are currently utilized by investigators around the world. He was recently head of R&D at Ring Therapeutics and was appointed as the inaugural director of the Gene and Cell Therapy Institute at Mass General Brigham. He has initiated multiple clinical trials in gene therapy for a variety of cardiovascular diseases, authored over 500 publications and received numerous awards for his achievements in the field of cardiac gene therapy. Dr. Hajjar is a co-founder of several biotechnology companies and was involved in the creation of multiple gene therapy companies at Flagship Pioneering, Cambridge, MA. Neha Motwani has over 25 years of healthcare investment banking experience, most recently having served as Managing Director, Healthcare Investment Banking at William Blair. She previously held investment banking roles of increasing responsibility with Truist Securities, Oppenheimer and Company, Stifel Financial and Cowen and Company, where, collectively, she completed transactions raising over $6.8 billion. Ms. Motwani earned her B.A in political science from Columbia University. About Longeveron Inc. Longeveron is a clinical stage biotechnology company developing regenerative medicines to address unmet medical needs. The Company’s lead investigational product is Lomecel-B™, an allogeneic medicinal signaling cell (MSC) therapy product isolated from the bone marrow of young, healthy adult donors. Lomecel-B™ has multiple potential mechanisms of action encompassing pro-vascular, pro-regenerative, anti-inflammatory, and tissue repair and healing effects with broad potential applications across a spectrum of disease areas. Longeveron is currently pursuing three pipeline indications: hypoplastic left heart syndrome (HLHS), Alzheimer’s disease, and Aging-related Frailty. For more information, visit www.longeveron.com or follow Longeveron on LinkedIn, X, and Instagram. Forward-Looking Statements Certain statements in this press release that are not historical facts are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, which reflect management’s current expectations, assumptions, and estimates of future operations, performance and economic conditions, and involve risks and uncertainties that could cause actual results to differ materially from those anticipated by the statements made herein. Forward-looking statements are generally identifiable by the use of forward-looking terminology such as “believe,” “expects,” “may,” “looks to,” “will,” “should,” “plan,” “intend,” “on condition,” “target,” “see,” “potential,” “estimates,” “preliminary,” or “anticipates” or the negative thereof or comparable terminology, or by discussion of strategy or goals or other future events, circumstances, or effects and include, but are not limited to, the anticipated use of proceeds from the private placement. Factors that could cause actual results to differ materially from those expressed or implied in any forward-looking statements in this release include, but are not limited to, market and other conditions, our limited operating history and lack of products approved for commercial sale; adverse global conditions, including macroeconomic uncertainty; inability to raise additional capital necessary to continue as a going concern; our history of losses and inability to achieve profitability going forward; the absence of FDA-approved allogenic, cell-based therapies for Aging-related Frailty, AD, or other aging-related conditions, or for HLHS or other cardiac-related indications; ethical and other concerns surrounding the use of stem cell therapy or human tissue; our exposure to product liability claims arising from the use of our product candidates or future products in individuals, for which we may not be able to obtain adequate product liability insurance; the adequacy of our trade secret and patent position to protect our product candidates and their uses: others could compete against us more directly, which could harm our business and have a material adverse effect on our business, financial condition, and results of operations; if certain license agreements are terminated, our ability to continue clinical trials and commercially market products could be adversely affected; the inability to protect the confidentiality of our proprietary information, trade secrets, and know-how; third-party claims of intellectual property infringement may prevent or delay our product development efforts; intellectual property rights do not necessarily address all potential threats to our competitive advantage; the inability to successfully develop and commercialize our product candidates and obtain the necessary regulatory approvals; we cannot market and sell our product candidates in the U.S. or in other countries if we fail to obtain the necessary regulatory approvals; final marketing approval of our product candidates by the FDA or other regulatory authorities for commercial use may be delayed, limited, or denied, any of which could adversely affect our ability to generate operating revenues; we may not be able to secure and maintain research institutions to conduct our clinical trials; ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations; if we receive regulatory approval of Lomecel-B™ or any of our other product candidates, we will be subject to ongoing regulatory requirements and continued regulatory review, which may result in significant additional expense; being subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our therapeutic candidates; reliance on third parties to conduct certain aspects of our preclinical studies and clinical trials; interim, “topline” and preliminary data from our clinical trials that we announce or publish from time to time may change as more data become available and are subject to audit and verification procedures that could result in material changes in the final data; the volatility of price of our Class A common stock; we could lose our listing on the Nasdaq Capital Market; provisions in our certificate of incorporation and bylaws and Delaware law might discourage, delay or prevent a change in control of our company or changes in our management and, therefore, depress the market price of our Class A common stock; we have never commercialized a product candidate before and may lack the necessary expertise, personnel and resources to successfully commercialize any products on our own or together with suitable collaborators; and in order to successfully implement our plans and strategies, we will need to grow our organization, and we may experience difficulties in managing this growth. Further information relating to factors that may impact the Company’s results and forward-looking statements are disclosed in the Company’s filings with the Securities and Exchange Commission, including Longeveron’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission on February 27, 2024, as amended by the Annual Report on Form 10-K/A filed March 11, 2024, its Quarterly Reports on Form 10-Q, and its Current Reports on Form 8-K. The forward-looking statements contained in this press release are made as of the date of this press release, and the Company disclaims any intention or obligation, other than imposed by law, to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. Investor Contact: Derek Cole Investor Relations Advisory Solutions derek.cole@iradvisory.com